This P30 Cystic Fibrosis (CF) Research and Translational Core Center (CFRTC) is located at the University of Washington School of Medicine (UWSOM) and its affiliated institution, Seattle Children's Research Institute (SCRI). This proposed P30 center program enhances an existing robust basic and clinical research base at these institutions totally over $20 million direct costs in current research funding and an additional $5 million in CF related infrastructure funding, and includes 48 UWSOM investigators in 19 departments and/or divisions. The UWSOM has a long history of excellence in CF related translational research as evidenced by the successful development of inhaled tobramycin (TOBI(r)) and the leadership in the CFF supported Therapeutics Development Network. The research for this P30 will focus on four Specific Aims: 1) Provide resources and expertise to expedite development of promising new therapeutic approaches to correct dysfunctional CFTR and its secondary consequences including maldigestion and malnutrition, hepatobiliary disease and chronic lung disease. 2) Foster collaboration across P-30 biomedical cores, nationally and internationally to enhance translational research through sharing of human and bacterial repositories linked to clinical databases. Utilize these shared specimen and data resources to develop improved assays, biomarkers and clinical outcome measures. 3) Enhance understanding of the evolving bacterial ecosystems and resultant host response in the gastrointestinal and respiratory tracts of patients with cystic fibrosis and how these interactions impact health. 4) Better understand the metabolic and inflammatory consequences of CFTR dysfunction. The center will be led by Co-PD's, Bonnie Ramsey, MD and E. Peter Greenberg PhD, CF investigators both internationally recognized in their respective areas of clinical research and bacterial pathogenesis. They will be supported by other key leadership: Samuel Miller MD, Professor of Medicine, Microbiology, Genome Sciences, and Immunology, Charles Frevert, DVM, ScD, Associate Professor in the Department of Comparative Medicine, Christopher Goss MD, MPH, Professor of Medicine and Pediatrics, and Pradeep Singh MD, Professor of Medicine. The center will consist of an Administrative Core (Ramsey and Greenberg, Directors) and four biomedical cores, Microbiology (Greenberg, Director), Genomics (Miller, Director), Host Response (Frevert, Director) and Clinical Translational (Christopher Goss and Ramsey, Directors). The core centers will operate a Pilot and Feasibility (P&F) program led by Dr. Pradeep Singh. Three newly approved P&F projects are included in the current proposal chosen through a competitive process and approved by the Internal Advisory Board. During the funding period, the core center will focus on development of several novel therapeutic approaches to improve overall health for patients with CF.